TABLE 1.

Summary of distinct studies and observations, including retrospective, prospective or randomized‐controlled trials published or in perspective of enrollment using anticoagulation and/or oxygen hyperbaric therapy

Authors	Country	Study design	Heparin	Warfarin	DOACs	Hyperbaric oxygen therapy (HBOT)
Tang et al 37	China	Retrospective	99 inpatients between 499 with severe COVID‐19 received heparin (mainly with low molecular weight heparin) for 7 days or longer. D‐dimer, prothrombin time, and age were positively, and platelet count was negatively, correlated with 28‐day mortality in multivariate analysis. No difference in 28‐day mortality was found between heparin users and non‐users (30.3% vs 29.7%, P = .910). But the 28‐day mortality of heparin users was lower than non‐users in patients with SIC (sepsis‐induced coagulopathy) score ≥ 4 (40.0% vs 64.2%, P = .029), or D‐dimer >6‐fold of upper limit of normal (32.8% vs 52.4%, P = .017).
Ayerbe et al 38	Spain	Retrospective	2075 patients in 17 Spanish hospitals between first March and the 20th of April 2020. Several treatments were applied (heparin, hydroxychloroquine, azithromycin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir). Heparin was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI) 0.55 (0.37‐0.82) P = .003. This association remain significant when saturation of oxygen < 90%, and temperature > 37°C were added to de model with OR 0.54 (0.36‐0.82) P = .003, and also when all the other drugs were included as covariates OR 0.42 (0.26‐0.66) P < .001.
Marietta et al 29	Italy	Prospective. Protocol version 1.2 of 11/05/2020. Recruitment start (expected): 08/06/2020 Recruitment finish (expected): 30 April 2021 Trial registration EudraCT 2020‐001972‐13, registered on 17 April, 2020	Inpatients will be recruited from 7 Italian Academic and non‐Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit. Control Group (Low‐Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (ie, 4000 UI subcutaneously once day). Intervention Group (High‐Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa) at dose of 70 IU/kg every 12 hours.
Wilkinson et al 39	United Kingdom	Prospective. EudraCT 2020‐001736‐95, registered 28 April 2020.	ACCORD is a seamless, Phase 2, adaptive, randomized controlled platform study, designed to rapidly test candidate agents in the treatment of COVID‐19. Current candidate experimental arms include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulized heparin with others to be added over time.
Busani et al 40	Italy	Prospective. Inpatients will be recruited from 8 Italian Academic and non‐Academic Intensive Care Units	Recruitment of 210 participants will be completed in approximately 10 months. Three groups of patients: (1) LMWH (low molecular weight heparin) group: patients in this group will be administered enoxaparin at standard prophylactic dosage. (2) LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. (3) UFH (unfractionated heparin) + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone.
Kharma et al 41	Qatar	Prospective. Single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. ANTI‐CO Trial” in ClinicalTrials.org with the registration number: NCT04445935. Registered on June 24, 2020.	The authors will enroll a total of 100 patients (50 in each group). The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45‐70 seconds for three days while the control group will stay on the standard treatment with low‐molecular‐weight heparins /unfractionated heparin subcutaneously
Barco et al 42	Switzerland	Prospective. OVID study. RCT, open‐label study, no blinding procedures will be used.	1000 patients: 500 patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4000 IU anti‐Xa activity (40 mg/0.4 mL) once daily for 14 days. Other 500 patients randomized to the comparator group will receive no anticoagulation.
				None study
Testa et al 43	Italy	Observational. Patients hospitalized between February 22 and March 15.			Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID‐19 pneumonia and candidates for antiviral therapy (lopinavir, ritonavir, or darunavir), 32 were on treatment with a DOAC (dabigatran apixaban, rivaroxaban and edoxaban). DOAC was stopped in 20 and continued in the remaining 12. On average, C‐trough levels were 6.14 times higher during hospitalization than in the pre‐hospitalization period. DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels.
New York University Winthrop Hospital. 15	USA	Prospective. Open Label Single‐Center Study of Emergency Hyperbaric Oxygen for Respiratory Distress in patients with COVID‐19. NYU Winthrop Hospital. ClinicalTrials.gov identifier NCT04332081				Standard treatment plus HBOT for 40 COVID19‐positive patients with respiratory distress. The patient will receive 90 minutes of hyperbaric oxygen at 2.0 ATA with or without airbreaks per the hyperbaric physician.